This invention relates to novel compounds, pharmaceutical compositions and a method of inhibiting the 5-lipoxygenase pathway of arachidonic acid metabolism in an animal in need thereof which comprises administering to such animal an effective, 5-lipoxygenase pathway inhibiting amount of a 2,2-[1,2-ethanediyl-bis-(thio)-bis-1H-imidazole, a 2,2-[1,3-propan-2-onediylbis-(thio)]bis-1H-imidazole or a pharmaceutically acceptable salt thereof.
Hill, U.S. Pat. No. 4,188,397, issued Feb. 12, 1980 discloses compounds of the formula ##STR1## wherein: R is 4-monosubstituted phenyl wherein said substituent is selected from methoxy, methylthio, trifluoromethyl, chloro, fluoro, bromo or methylenedioxy when taken with an adjacent position on the phenyl ring;
R.sup.2 and R.sup.3 are both H or one is H and the other is CH.sub.3 ; PA0 n is 0, 1 or 2; and PA0 X is, among others, (CH.sub.2).sub.2 and CH.sub.2 C (O)CH.sub.2. PA0 R.sup.11 and R.sup.111 are both pyridyl or one of R.sup.11 and R.sup.111 is pyridyl and the other is monosubstituted phenyl wherein said substituent is selected from halo; or a pharmaceutically acceptable salt thereof. PA0 R and R.sup.1 are independently selected from pyridyl or monosubstituted phenyl wherein said substituent is selected from halo; or a pharmaceutically acceptable salt thereof.
Hill also discloses that such compounds are useful as antiarthritic agents, as confirmed by their ability to inhibit adjuvant induced polyarthritis in rats; and are also useful to regulate cell mediated immunity, as confirmed by the oxazolone-induced contact sensitivity test procedure which measures changes in mouse paw edema produced by administration of test compounds.
The adjuvant-induced polyarthritis assay in rats is useful in detecting compounds which are inhibitors of prostanoid synthesis, mediated by the prostanoids formed by the enzyme cyclooxygenase, but is of no known utility in detecting or suggesting compounds which are inhibitors of the generation of 5-lipoxygenase products (such as HETES, LTB.sub.4 and peptidoleukotrienes). The oxazolone-induced contact sensitivity test in which mouse paw volume is measured is useful in detecting compounds which are immunostimulatory, but is of no known utility in detecting or suggesting compounds which are inhibitors of the 5-lipoxygenase pathway.